组蛋白乙酰化修饰H4K16ac参与乳腺癌细胞Notch1致瘤信号传递

Histone Acetylation Modification H4K16ac Involved in Notch1 Signaling Pathway in Breast Cancer

Notch1信号通路在调节细胞的增殖、分化和凋亡中起重要作用。Notch1信号通路的异常激活可促进乳腺癌的发生、发展,但调控此过程的表观遗传机制尚有待于阐明。本研究发现,与相应的癌旁组织相比,乳腺癌组织中Notch1活性片段NIC1呈高表达,而组蛋白H4第16位赖氨酸残基乙酰化(H4K16ac)水平较低。敲低MCF-7细胞中Notch1可导致H4K16ac水平升高,且MCF-7细胞的增殖和迁移能力下降。本研究结果提示表观遗传修饰H4K16ac参与乳腺癌细胞Notch1致瘤信号传递,为乳腺癌发生、发展的机制研究提供了新思路。

The Notch1 signaling pathway plays an important role in the regulation of cell proliferation,differentiation and apoptosis. The abnormal activation of Notch 1 signaling pathway can promote the development of breast cancer. The abnormal activation of Notch1 signaling pathway can promote the occurrence and development of breast cancer, however, the epigenetic mechanism which regulating the process remains to be elucidated. In this study, compared with corresponding adjacent cancer tissues, Notch 1 active fragment NIC1 was highly expressed in breast cancer tissues, instead the level of histone H4 sixteenth lysine residues（H4K16ac） was much lower. Knocking down the Notch1 in MCF-7 cells can elevate the level of H4K16 ac, as well as decrease the proliferation and migration ability of MCF-7 cells. The results of this study suggested that epigenetic modification of H4K16 ac was involved in the tumorigenesis signal transduction of Notch1 in breast cancer cells, which provided a new idea for the study on occurrence and development mechanisms of breast cancer.